Radiolabelling is fundamental in drug discovery and development as it is mandatory for preclinical ADME studies and late‐stage human clinical trials. Herein, a general, effective, and easy to implement method for the multiple site incorporation of deuterium and tritium atoms using the commercially available and air‐stable iridium precatalyst [Ir(COD)(OMe)]₂ is described. A large scope of pharmaceutically relevant substructures can be labelled using this method including pyridine, pyrazine, indole, carbazole, aniline, oxa‐/thia‐zoles, thiophene, but also electron‐rich phenyl groups. The high functional group tolerance of the reaction is highlighted by the labelling of a wide range of complex pharmaceuticals, containing notably halogen or sulfur atoms and nitrile groups. The multiple site hydrogen isotope incorporation has been explained by the in situ formation of complementary catalytically active species: monometallic iridium complexes and iridium nanoparticles.

中文翻译：

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药物的多位氢同位素标记

放射性标记是药物发现和开发的基础，因为它是临床前ADME研究和晚期人体临床试验所必需的。在此，使用可商购的且空气稳定的铱预催化剂[Ir（COD）（OMe）] ₂进行氘和tri原子多位掺入的通用，有效且易于实施的方法描述。使用此方法可以标记许多与药物相关的亚结构，包括吡啶，吡嗪，吲哚，咔唑，苯胺，氧杂/噻唑，噻吩，以及富电子的苯基。反应的高官能团耐受性通过多种复杂药物的标记突出显示，这些药物特别包含卤素或硫原子和腈基。多位氢同位素掺入已经通过互补催化活性物质的原位形成来解释：单金属铱络合物和铱纳米粒子。